A Review of Post-Operative Drops used in Cataract Surgery
Cataracts affect an estimated 95 million people worldwide and about 10 million surgeries are performed annually to correct them.  This makes cataract surgery one of the most common procedures performed in the world. It is a relatively safe procedure performed in the outpatient setting and patients are typically given a variety of topical eye drop medications to take to prevent various postoperative complications. The most common complications can include post-operative as well as sustained corneal edema, development of CEIOL induced cystoid macular edema, and endophthalmitis. There is little data to suggest a optimal postoperative drop regimen, and so the frequency of use and choice of drugs vary among practitioners. The typical drug classes prescribed include topical antibiotics, NSAIDs, and corticosteroids.
The goal of topical antibiotics is to prevent the development of postoperative endophthalmitis. This occurs in 0.006-0.04% of patients following cataract surgery and carries a very high morbidity. Given how rare it is, few randomized controlled trials have been performed to clearly establish the benefit of postoperative antibiotic drops in preventing this complication. Still, as these are generally low risk drugs, nearly all patients are placed on topical antibiotics following cataract surgery. The most prescribed drugs are the 4th generation fluoroquinolones, gatifloxacin and moxifloxacin. These provide optimal coverage for the most implicated pathogens: coagulase-negative staphylococci, staphylococcus aureus, and streptococci. They also provide the added benefit of improved ocular penetration compared to other topical antibiotics. Additionally, some surgeons have begun to use intracameral injections of cefuroxime intraoperatively to further reduce risk. This form of antibiotic involves the injection of drug into either the anterior or posterior chambers of the eye. In a review of 5 studies including over 100,000 adults total, the Cochrane group concluded that there is high-certainty evidence suggesting that this treatment modality with or without postoperative levofloxacin decreases the risk of endophthalmitis following cataract surgery. Unfortunately, there are no commercially approved formulations in the United States, hence why most surgeons have yet to adopt this treatment modality.
Topical NSAIDs have been used in the pre-operative, peri-operative and post-operative settings for their multifaceted effect. Current research shows that NSAIDs are effective in maintaining pupillary dilation intra-operatively as well as reducing the incidence of cystoid macular edema (CME) when combined with corticosteroids postoperatively.
CME is caused by the intraocular inflammation induced by surgery and occurred at a rate of 3.3% between the years of 2005-2007. While CME occurs infrequently after routine uncomplicated small-incision cataract surgery and often responds well to medical therapy, it may be associated with permanent impairment of central visual acuity. A suggested therapeutic scheme for CME prevention includes one drop of NSAIDs four times a day, beginning the day before surgery and for four weeks following the procedure. Further schemes include administering one drop of topical NSAIDs every 15 minutes in the hour prior to surgery for anti-inflammatory effects. Typical drops used include Bromofenac 0.09% (BID), Nepafenac 0.1% (TID), Ketorolac (QID), Diclofenac (QID). 
Beyond their role in CME prevention and inhibition of miosis during cataract surgery, NSAIDs are not proven to improve visual outcomes. Further, there is similar incidence of lid edema, lid injection, conjunctival injection, corneal edema, ciliary flush and anterior chamber cells in patients receiving topical NSAIDs vs. topical corticosteroids, suggesting that both treatments are effective. The adverse effects of NSAIDs include corneal melt in the setting of epithelial breakdown and enhancement of the severity of postoperative dry eye. The postoperative ocular surface effects are believed to be related to aggravated hypesthesia in patients with dry eye. The use of NSAIDs is based on provider discretion, as evidence of the benefits and risks continues to emerge.
Inflammatory effects of cataract surgery are also the targets of topical corticosteroids. Patients who have increased risk of postoperative inflammation include those with longer operative times, period surgery and extensive procedures at a younger age. The effects of topical corticosteroids on postoperative outcomes include decreasing post-surgical incidence of CME and reducing inflammation such as lid edema, lid injection, conjunctival injection, corneal edema, ciliary flush, and anterior chamber cells. Of note, corticosteroids are particularly effective in controlling inflammation in patients with uveitis. Evidence suggests that NSAIDs and corticosteroids are synergistic in the prevention of CME. Studies comparing topical NSAIDs to topical corticosteroids indicate that outcomes in ocular inflammation are statistically insignificant, however corticosteroids have been shown to be more effective in reducing the number of cells in the anterior chamber in the immediate post-operative setting. Steroid formulations include prednisolone 1%, rimexolone 1%, loteprednol etabonate 0.5% and difluprednate 0.05% and are typically prescribed in the postoperative setting for 2-6 weeks. Evidence further shows difluprednate to be effective in managing ocular inflammation, pain and discomfort postoperatively when used prophylactically 24 hours before surgery.
The most significant complication of corticosteroid use is increased intraocular pressure (IOP), which occurs more frequently in younger, highly myopic patients or those with glaucoma. Rimexolone 1% has been shown to have a decreased tendency to increase IOP, compared to prednisolone acetate 1%. Further, topical corticosteroids have been associated with hastened development of posterior subcapsular cataracts, and post-surgical bacterial and viral infections.  Overall, the benefits and risks of topical corticosteroids must be weighed by the operative surgeon when determining the ideal therapeutic regimen for each patient.
Topical Dry Eye Therapy
Another complication patients often deal with following cataract surgery is Dry eyes. Several aspects about the management of cataracts can predispose patients to Dry Eye Disease (DED). These include corneal nerve injury, irritation from repeated cycles of drying and irrigation intraoperatively, phototoxicity from the microscope, and toxic effects of postoperative cataract drops. This can cause significant morbidity to patients as DED can lead to symptoms ranging from irritation and hyperemia to blurry vision and decreased visual acuity. As one of the goals of CEIOL is to improve vision, postoperative DED can be a source of frustration to patients. To counter this, patients and providers have several treatment options at their disposal.
The first would be to advise patients to avoid environments or substances that may provoke symptoms. This can include avoiding smoke, dust, or direct air conditioning as well as limiting screen time, alcohol intake, or cigarette smoking (Clayton). In terms of topical treatments, first line therapy typically consists of a regimen of either artificial tears, gels, or ointments. These treatments lubricate the ocular surface and can help augment the tear film that becomes dysfunctional in DED. Preservative-free formulations are typically favored if artificial tears are required as these have been shown to lack the toxic effects on the ocular surface that certain preservative containing drops have (Baudoin).
Additionally, physicians may also prescribe a two-to-four-week regimen of topical cyclosporine. This drug acts to decrease ocular surface inflammation and improve lacrimal gland function, thus improving tear production and minimizing symptoms of DED. If response to these treatments remains poor, other agents are available. These include diquafasol sodium (DQS), a P2Y2 agonist, and rebamipide, a quinolone derivative. These drugs act to increase mucin secretion into the tear film, thus stabilizing tears and preserving their ocular protective effects. They have been shown to effectively decrease the symptoms and incidence of DED following cataract surgery.
Drops for the management of complicated cataract removal
Though intraoperative complications during cataract surgery are rare, they do present additional challenges for postoperative management. These complications can include patient factors such as a miotic pupil or a mature cataract, both of which impair operative visibility and require additional operative interventions for successful cataract removal, or operative ones such as a posterior capsule rupture or non-capsular lens placement. In these cases, patients will often develop more intense or prolonged inflammation postoperatively and may also experience intraocular pressure spikes. Thus, patients are at increased risk of developing future complications such as CME, glaucoma, endophthalmitis, or retinal detachment. To manage this, patients with complicated cataract surgeries are instructed to follow-up with their provider within 24 hours and are encouraged to return frequently for monitoring thereafter. Typically, providers will offer a similar drop regimen as described above. This includes topical NSAIDs and corticosteroids as well as either topical or oral antibiotics, depending on surgeon’s preference.
Some surgeons may also encourage patients to start on drops to prevent glaucoma. Though there has been no concrete evidence to suggest glaucoma drops can prevent intraocular pressure spikes postoperatively, some studies advocate for the use of topical brinzolamide, a carbonic anhydrase inhibitor (CAI), coupled with a dorzolamide/timolol combination drop, a CAI and beta-blocker, in those at high risk of developing glaucoma or in those with pre-existing optic nerve damage (Grzybowski 2017, Levkovitch-Verbin 2008, Hayashi 2019, Ermis 2005). In those with a miotic pupil, pilocarpine 1% or 2% may be added for an additional 1-2 weeks to augment pupillary healing postoperatively.
Cataract surgery is the most performed ophthalmic surgery, worldwide. Complications from this surgery vary widely. Postoperative topical eye drops are typically employed to prevent some of the more concerning complications, such as endophthalmitis or CME. These include a regimen of topical antibiotics, NSAIDs, corticosteroids, and artificial tears/mucin secretagogues. Fourth generation fluoroquinolones are typically the preferred antibiotic due to their broad-spectrum coverage and improved ocular penetration. Additionally, newer evidence supports the use of intracameral antibiotics intraoperatively to further reduce a patient’s risk of postoperative endophthalmitis. To prevent CME, NSAIDs and corticosteroids are employed concurrently to reduce the inflammation that predisposes patients to its development. And finally artificial tears or the newer mucin-stimulating agents are utilized to protect the ocular surface from irritation and decrease symptoms of DED. The exact formulation of drop and the amount of time they are prescribed typically depends on the preferences of the surgeon.
- ↑ 1.0 1.1 1.2 Liu YC, Wilkins M, Kim T, Malyugin B, Mehta JS. Cataracts. Lancet. 2017;390(10094):600-612. doi:10.1016/S0140-6736(17)30544-5.
- ↑ Foster A. Vision 2020: the cataract challenge. Community Eye Health 2000;13:17-9.
- ↑ Liesegang TJ. Use of antimicrobials to prevent postoperative infection in patients with cataracts. Curr Opin Ophthalmol. 2001;12(1):68-74.
- ↑ Shoss, Bradley L.; Tsai, Linda M. Postoperative care in cataract surgery, Current Opinion in Ophthalmology: January 2013 - Volume 24 - Issue 1 - p 66-73 doi: 10.1097/ICU.0b013e32835b0716.
- ↑ Han D.P., Wisniewski S.R., Wilson L.A., et. al.: Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study. Am J Ophthalmol 1996; 122: pp. 1-17.
- ↑ Chang DF, Braga-Mele R, Mamalis N, et al. Prophylaxis of postoperative endophthalmitis after cataract surgery: results of the 2007 ASCRS member survey. J Cataract Refract Surg 2007; 33:1801–1805.
- ↑ Gower EW, Lindsley K, Tulenko SE, Nanji AA, Leyngold I, McDonnell PJ. Perioperative antibiotics for prevention of acute endophthalmitis after cataract surgery. Cochrane Database of Systematic Reviews 2017, Issue 2. Art. No.: CD006364. DOI: 10.1002/14651858.CD006364.pub3. Accessed 31 October 2021.
- ↑ Haripriya A, Chang DF. Intracameral antibiotics during cataract surgery: evidence and barriers. Curr Opin Ophthalmol. 2018;29(1):33-39. doi:10.1097/ICU.0000000000000445.
- ↑ 9.0 9.1 9.2 McColgin AZ, Heier JS. Control of intraocular inflammation associated with cataract sur-gery. Curr Opin Ophthalmol. 2000;11(1):3-6.
- ↑ Greenberg PB, Tseng VL, of predictors ocular complications associated with cataract surgery in United States veterans. Ophthalmology 2011;118:507-14.
- ↑ 11.0 11.1 American Academy of Ophthalmology Cataract and Anterior Segment Panel. Preferred Practice Pattern Guidelines. Cataract in the adult eye. San Francisco, CA: American Academy of Ophthalmology; 2011.
- ↑ Quintana, N. E., Allocco, A. R., Ponce, J. A., & Magurno, M. G. (2014). Non steroidal anti-inflammatory drugs in the prevention of cystoid macular edema after uneventful cataract surgery. Clinical ophthalmology (Auckland, N.Z.), 8, 1209–1212. https://doi.org/10.2147/OPTH.S61604.
- ↑ 13.0 13.1 Quintana, N. E., Allocco, A. R., Ponce, J. A., & Magurno, M. G. (2014). Non steroidal anti-inflammatory drugs in the prevention of cystoid macular edema after uneventful cataract surgery. Clinical ophthalmology (Auckland, N.Z.), 8, 1209–1212. https://doi.org/10.2147/OPTH.S61604.
- ↑ 14.0 14.1 14.2 Chen, Sherleen H., et al. Essentials of Cataract Surgery, Second Edition. Vol. Second edition, SLACK Incorporated, 2014.
- ↑ 15.0 15.1 Kato K, Miyake K, Hirano K, Kondo M. Management of Postoperative Inflammation and Dry Eye After Cataract Surgery. Cornea. 2019;38 Suppl 1:S25-S33.
- ↑ 16.0 16.1 16.2 Shoss, Bradley L.; Tsai, Linda M. Postoperative care in cataract surgery, Current Opinion in Ophthalmology: January 2013 - Volume 24 - Issue 1 - p 66-73 doi: 10.1097/ICU.0b013e32835b0716.
- ↑ Simone JN, Pendelton RA, Jenkins JE: Comparison of the efficacy and safety of ketorolac tromethamine 0.5% and prednisolone acetate 1% after cataract surgery. J Cataract Refract Surg 1999, 25:699–704.
- ↑ Smith S, Lorenz D, Peace J, McLeod K, Crockett RS, Vogel R. Difluprednate ophthalmic emulsion 0.05% (Durezol) administered two times daily for managing ocular infl ammation and pain following cataract surgery. Clin Ophthalmol. 2010;7(4):983-991.
- ↑ Foster CS, Alter G, DeBarge LR, et al. Efficacy and safety of rimexolone 1% ophthalmic suspension vs 1% prednisolone acetate in the treatment of uveitis. Am J Ophthalmol. 1996;122(2):171-182.
- ↑ Naderi K, Gormley J, O'Brart D. Cataract surgery and dry eye disease: A review. Eur J Ophthalmol. 2020;30(5):840-855. doi:10.1177/1120672120929958.
- ↑ Clayton JA. Dry Eye. N Engl J Med. 2018;379(11):e19. doi:10.1056/NEJMc1808906
- ↑ Zhao X, Xia S, Chen Y. Comparison of the efficacy between topical diquafosol and artificial tears in the treatment of dry eye following cataract surgery: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2017;96(39):e8174. doi:10.1097/MD.0000000000008174.
- ↑ Shrivastava S, Patkar P, Ramakrishnan R, Kanhere M, Riaz Z. Efficacy of rebamipide 2% ophthalmic solution in the treatment of dry eyes. Oman J Ophthalmol. 2018;11(3):207-212. doi:10.4103/ojo.OJO_29_2017.
- ↑ Olson RJ, Braga-Mele R, Chen SH, et al. Cataract in the Adult Eye Preferred Practice Pattern®. Ophthalmology. 2017;124(2):P1-P119. doi:10.1016/j.ophtha.2016.09.027
- ↑ Grzybowski A, Kanclerz P. Do we need day-1 postoperative follow-up after cataract surgery?. Graefes Arch Clin Exp Ophthalmol. 2019;257(5):855-861. doi:10.1007/s00417-018-04210-0
- ↑ Levkovitch-Verbin H, Habot-Wilner Z, Burla N, et al. Intraocular pressure elevation within the first 24 hours after cataract surgery in patients with glaucoma or exfoliation syndrome. Ophthalmology. 2008;115(1):104-108. doi:10.1016/j.ophtha.2007.03.058
- ↑ Hayashi K, Yoshida M, Sato T, Manabe SI. Effect of Topical Hypotensive Medications for Preventing Intraocular Pressure Increase after Cataract Surgery in Eyes with Glaucoma. Am J Ophthalmol. 2019;205:91-98. doi:10.1016/j.ajo.2019.03.012
- ↑ Ermis, S., Ozturk, F. & Inan, U. Comparing the effects of travoprost and brinzolamide on intraocular pressure after phacoemulsification. Eye 19, 303–307 (2005). https://doi.org/10.1038/sj.eye.6701470